1. Extracellular signal-regulated kinase (ERK) activation is required for GP Ibalpha-dependent endothelial cell migration.
- Author
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Lian J, Marcinkiewicz C, Niewiarowski S, and Beacham DA
- Subjects
- Antibodies, Monoclonal pharmacology, Cell Movement drug effects, Cells, Cultured drug effects, Cells, Cultured metabolism, Collagen antagonists & inhibitors, Crotalid Venoms pharmacology, Endothelium, Vascular cytology, Endothelium, Vascular drug effects, Enzyme Activation drug effects, Enzyme Inhibitors pharmacology, Humans, Integrins antagonists & inhibitors, Intercellular Signaling Peptides and Proteins, MAP Kinase Signaling System drug effects, Mitogen-Activated Protein Kinase 3, Peptides pharmacology, Platelet Glycoprotein GPIb-IX Complex antagonists & inhibitors, Platelet Glycoprotein GPIb-IX Complex immunology, Receptors, Collagen, Receptors, Fibronectin antagonists & inhibitors, Receptors, Vitronectin antagonists & inhibitors, von Willebrand Factor antagonists & inhibitors, Endothelium, Vascular enzymology, MAP Kinase Signaling System physiology, Mitogen-Activated Protein Kinase 1 metabolism, Mitogen-Activated Protein Kinases metabolism, Platelet Glycoprotein GPIb-IX Complex physiology
- Abstract
The GP Ib complex can participate in endothelial cell (EC) migration on von Willebrand factor (vWF) or the mixed matrix of vWF and type I collagen (vWF/collagen). In this study, viper venom proteins alboaggregin (albo) A or B blocked GP Ibalpha, and echistatin inhibited alphavbeta3 binding. Albo A, B and echistatin inhibited EC migration on vWF and vWF/collagen. Albo B or the anti-GP Ibalpha monoclonal antibody (mAb) 1b1 did not affect the migration of smooth muscle cells or fibroblasts, which lack GP Ib. EC also migrate on albo A- or albo B-coated dishes. PD98059, which blocks ERK activation, abolished EC migration on vWF, vWF/collagen, collagen or albo B. Soluble albo A or 1b1 dramatically inhibited ERK activation during EC migration on vWF or albo B. Echistatin inhibited ERK activation on vWF and vitronectin (VN), but not albo B. Thus, in addition to alphavbeta3, EC GP Ibalpha initiates ERK activation, and regulates ERK-induced EC migration on vWF.
- Published
- 2001